Our work is directed toward a detailed understanding of the interactions between heterogeneous nuclear RNA and the structural proteins with which it associates. In this study, we propose to carry out a detailed analysis of the thermodynamic and structural properties of the interaction between nucleic acids and the protein HD40. HD40 is the single major protein component of the hnRNP complexes in the brine shrimp Artemia salina. It is the first major hnRNP protein to have been purified in large quantities in a nondenatured state, and provides the best system available for investigating the fundamental properties of the hnRNP complexes. HD40 incorporates both helix destabilizing and nucleic acid compacting activities into a single polypeptide chain. At stoichiometries up to 1 protein per 12 nucleotides, HD40 acts as a helix destabilizing protein. Then, at higher stoichiometries, the unfolded nucleic acid protein complex is condensed, acquiring a "bead-on-string" appearance that is similar to that of native hnRNP complexes. We now have evidence to suggest that the complex set of hnRNP proteins from higher eukaryotes also has these general nucleic acid binding properties, and we believe that a detailed description of the HD40-nucleic acid interaction will provide us with valuable insight into the properties of hnRNP complexes in general. Using standard biophysical methods, we will determine the thermodynamic parameters of the protein-nucleic acid and protein-protein interactions involved in the binding, and will investigate the effects of buffer conditions and nucleic acid composition on these parameters. The structural properties of the "beads-on-a-string" complex will be analyzed in terms of both the RNA and protein components through experiments employing electron microscopy and other standard bio-physical methods. We will use this information, together with data from related studies, to identify the basic structural features of hnRNP complexes.